research article donor heart utilization following...

Research ArticleDonor Heart Utilization following Cardiopulmonary Arrestand Resuscitation: Influence of Donor Characteristics and WaitTimes in Transplant Regions

Mohammed Quader, Luke Wolfe, Gundars Katlaps, and Vigneshwar Kasirajan

Department of Cardiothoracic Surgery, Virginia Commonwealth University, Richmond, VA 23298, USA

Correspondence should be addressed to Mohammed Quader; [email protected]

Received 5 May 2014; Accepted 20 June 2014; Published 8 July 2014

Academic Editor: Parmjeet Randhawa

Copyright © 2014 Mohammed Quader et al. This is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properlycited.

Background. Procurement of hearts from cardiopulmonary arrest and resuscitated (CPR) donors for transplantation is suboptimal.We studied the influences of donor factors and regional wait times on CPR donor heart utilization. Methods. From UNOSdatabase (1998 to 2012), we identified 44,744 heart donors, of which 4,964 (11%) received CPR. Based on procurement of heart fortransplantation, CPR donors were divided into hearts procured (HP) and hearts not procured (HNP) groups. Logistic regressionanalysis was used to identify predictors of heart procurement. Results. Of the 4,964 CPR donors, 1,427 (28.8%) were in the HPgroup. Donor characteristics that favored heart procurement include younger age (25.5± 15 yrs versus 39± 18 yrs, 𝑃 ≤ 0.0001),male gender (34% versus 23%, 𝑃 ≤ 0.0001), shorter CPR duration (<15min versus >30min, 𝑃 ≤ 0.0001), and head trauma (60%versus 15%). Among the 11 UNOS regions, the highest procurement was in Region 1 (37%) and the lowest in Region 3 (24%).Regional transplant volumes andmedian waiting times did not influence heart procurement rates. Conclusions. Only 28.8% of CPRdonor hearts were procured for transplantation. Factors favoring heart procurement include younger age, male gender, short CPRduration, and traumatic head injury. Heart procurement varied by region but not by transplant volumes or wait times.

1. Introduction

For patients with advanced heart failure awaiting hearttransplantation (HTx), donor heart supply remains a limitingfactor in offering the ultimate treatment option. Efforts tooptimize management of potential heart donors have led toincreased utilization of donor hearts [1], yet this increasefalls far short of the existing demands on organs for trans-plantation [2]. New avenues that would increase availabledonor hearts have been explored, including donation aftercardiac death [3], ex vivo organ resuscitation [4], and,importantly, extended donor selection criteria [5]. Of theseextended criteria, cardiopulmonary arrest and resuscitated(CPR) organ donors have significantly increased the potentialorgan donor pool. In the past decade alone, there has beena 90% increase in the number of organ donors who weresuccessfully resuscitated after cardiopulmonary arrest [2](Figure 1). We previously reported that the clinical outcomes

of heart transplantation from CPR donors are similar to theoutcomes from non-CPR donors [6]. This finding was alsonoted in other solid organ transplantation studies [7, 8].

Despite these encouraging reports, utilization of CPRdonor hearts has been less than 30% [2]. The reasons aremultifactorial, including concerns regarding warm ischemicdamage to organs sustained during cardiopulmonary arrest[9], nonuniform donor selection criteria among transplan-tation centers, acuity of illness of the organ recipients, and,perhaps, the overall transplant volumes and experiences.Most published studies on this subject have focused on therecipient outcomes with donor variables studied primarilyto predict posttransplantation outcomes [10, 11]. Our studyprincipally focuses on the donor variables, with the aimof identifying CPR donor characteristics predictive of heartprocurement for transplantation.We also sought to study theinfluences of 11UNOS regional heart transplantation volumesand regional wait times on CPR donor heart utilization.

Hindawi Publishing CorporationJournal of TransplantationVolume 2014, Article ID 519401, 7 pageshttp://dx.doi.org/10.1155/2014/519401

2 Journal of Transplantation

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10

(%)

Year

CPR donor % of the total donor pool

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

2011

2012

Figure 1: CPR donor percentage of the total heart donors.

UNOS regional map

Figure 2: UNOS 11 heart transplantation regions in USA.

2. Material and Methods

We examined the UNOS heart donor data between 1998and 2012 and identified 44,744 consented heart donors, ofwhich 4,964 (11%) were from CPR donors. This comprisedour study group, which was further divided into two groupsbased on heart procured (HP) or heart not procured (HNP)for transplantation. Besides donor demographics, data oncomorbid conditions, social history, causes of death, andduration of CPR were collected in a deidentified fashion foranalysis (Table 1). Data on 11 UNOS transplantation regions(Figure 2) were gathered and analyzed for transplantationvolumes, median 1A status wait times for heart transplanta-tion, and percent CPR donor heart utilization (Table 2).

Numeric data were analyzed and reported as mean,median, and standard deviations. A 𝑃 value of less than 0.05is considered statistically significant. Continuous variableswere analyzed with Student’s 𝑡-test; categorical variableswere analyzed with the chi-square test. A logistic regressionanalysis of 11 donor variables was performed to identifypredictors of heart procurement for transplantation from theCPR donor pool. The results of this regression analysis arereported as odds ratios with confidence limits.

3. Results

During the study period of 1998 to 2012, a total of 44,744 con-sented heart donors were identified in the UNOS database.

Table 1: CPR donor characteristics.

Donor variable

Heart procured for transplantation

𝑃 valueYes No𝑁 = 1,427(28.8%)

𝑁 = 3,537(67.2%)

Age in years 25.5 ± 15 yrs 39 ± 18 yrs <0.0001Gender <0.0001

Male 34 66Female 23 77

Duration of CPR <0.0001<15min 31 6915–30min 29 71>30min 25 75

Cause of Death <0.0001Head trauma 60 40Anoxia 29 71Cerebrovascular/stroke 15 85

Ethnicity <0.0001Hispanic 37 63Black 33 67White 27 73Asian 24 76

Donor ABO <0.0001O 32 68A 27 73B 24 76AB 15 85

Hypertension <0.0001Yes 12 88No 35 65

Social historyCigarette use <0.0001

Yes 17 83No 34 66

Heavy ETOH use 0.0001Yes 22 78No 30 70

UNOS region <0.00751 37 633 24 76

3 or more inotropicagents at the time ofincision

<0.0001

Yes 12 88No 30 70

LV ejection fraction% 61.4 ± 9.0 48.2 ± 17.3 <0.0001

CPR: cardiopulmonary resuscitation; ABO: blood groups; ETOH: alcohol;UNOS: United Network of Organ Donation; LV EF: left ventricle ejectionfraction.

Of which, 4,964 (11%) donors sustained cardiopulmonaryarrest and were resuscitated to spontaneous rhythm and

Journal of Transplantation 3

Table 2: Heart transplantation volumes, median wait times, and CPR donor heart procured for transplantation by 11 UNOS regions.

Region Total population Population/HTx Mean HTx volume/yr Median 1A wait time in days CPR donor utilization-%1 13,936,692 158,371 88 59.6 372 30,917,426 110,026 281 74.3 293 48,262,570 165,851 291 40 244 29,874,023 140915 212 47.6 275 52,294,441 155,176 337 34.6 326 15,521,147 242,517 64 72.6 267 25,513,744 125,683 203 90.3 308 19,601,598 141,018 139 80.3 309 20,196,272 133,750 151 58.3 2910 27,974,919 136,463 205 68.6 2811 33,498,321 140,160 239 67.6 31HTx: heart transplantation; CPR: cardiopulmonary resuscitation.

circulation. Only 1,427 (28.8%) of these CPR donor heartswere procured for transplantation; these donors comprisedthe hearts procured (HP) group.

When compared to the hearts not procured group, thehearts procured group were relatively younger (25 ± 15 yearsversus 39 ± 18 years, 𝑃 ≤ 0.0001) and a high proportionof them were male gender (34% M, versus 23% F, 𝑃 ≤0.0001). Cause of death influenced the percent utilizationof CPR donor hearts: those with head trauma leading tobrain death were selected more often for heart procurementcompared to those with intracerebral bleed (60% and 15%,resp., 𝑃 ≤ 0.0001). Similarly, mechanism of death played arole in the selection of CPR donors for heart procurement:those with gunshot wounds (44%), asphyxiation (40%), orblunt trauma (39%) were more often selected for heartprocurement compared to those with stroke (15%). CPRdonors with a history of hypertension were selected less oftenfor heart procurement, as only 12% of the hearts procuredgroup had a history of hypertension, compared to 35% in thehearts not procured group (𝑃 ≤ 0.0001). Ethnicity and thesocial history of the CPR donor were also factored into theheart procurement for transplantation (Table 1). Notably, ahigher percentage of donors with Hispanic ethnicity (37%)were accepted for heart procurement compared to only 24%for Asian ethnicity (𝑃 ≤ 0.0001). We noticed that there was ahigher prevalence of head trauma (35%), male gender (62%),and blood group O (60%) in Hispanic ethnicity heart donorscompared to other heart donors. Donors with a history oftobacco abuse (17%) and heavy alcohol consumption (22%)were less often selected for heart procurement. Durationof CPR also contributed significantly to the selection ofdonor heart for transplantation. Those donors with a CPRduration of less than 15min were selected more often forheart procurement than those with a CPR duration of greaterthan 30min (31% and 25%, resp., 𝑃 ≤ 0.0001). Left ventricleejection fraction (EF) was near normal in heart procuredgroup compared to heart not procured group, 61.4±9.0 versus48.2 ± 17.3, 𝑃 < 0.0001.

Data on regional heart transplantation volumes, waittimes on the transplantation list, and CPR donor heartutilization were also studied (Table 2). Heart transplantation

volumes, measured as the mean number of transplantationsperformed per year, varied between the 11 UNOS regions,from 64 in Region 6 to 337 in Region 5. Median wait timeson status 1A listing also varied significantly between theregions and did not correlate with transplantation volumes.The longestmedianwait timewas noted in Region 7 (90 days)while the shortest was in Region 5 (35 days).

CPR donor heart utilization varied significantly betweenthe eleven regions, with a low of 24% in Region 3 to a high of37% in Region 1 (𝑃 ≤ 0.0001). We also evaluated the CPRdonor utilization by population per heart transplantationperformed in the 11 regions. Region 6 had the highestpopulation per heart transplant (242,517/HTx), while thelowest was in Region 2 (110,026/HTx). CPRdonor utilizationsin Regions 6 and 2 were 26% and 29%, not statisticallysignificant.

Logistic regression analysis using heart procurement fortransplantation from CPR donors as an outcome variablewas studied factoring in eleven donor variables, includingregional transplant volumes, and wait times on transplanta-tion list (Table 3). CPR donor characteristics associated withheart procurement for transplantation by logistic regressionanalysis include younger donor age, male gender, shorterCPR duration, head trauma as a cause of death versuscerebrovascular accident, Hispanic ethnicity, blood groupO, and location in Region 1. Factors that were negativelyassociated with heart procurement for transplantation wereneed formultiple inotropes at the time of organ procurement,history of substance abuse, nontraumatic injuries leading tobrain death, low EF, and location in Region 3 (Table 3).

4. Comment

Since the limiting factor in offering heart transplantation topatients with advanced heart failure is a suitable heart donor,we embarked on studying a group of underutilized potentialheart donors: those who sustained cardiopulmonary arrestand were resuscitated. Our study demonstrates that CPRdonors that are younger, are male, incurred head trauma,received shorter duration CPR, and did not smoke or abusealcohol are selectedmore often for heart procurement.Wedid


Table 3: CPR donor variables that are predictive of successful heartprocurement for transplantation by logistic regression analysis.

Donor variable Odds ratio 95% confidencelimits P value

Age in years 1.033 1.028–1.038 <0.0001Gender

Female versus male 1.470 1.272–1.699 <0.0001Comorbidities

Hypertension: yesversus no 1.981 1.591–2.467 <0.0001

Duration of CPR 1.013 1.008–1.017 <0.0001Cause of death versushead trauma

Anoxia 1.118 0.945–1.322 0.2190Cerebrovascular/stroke 1.445 1.147–1.820 0.5109

Ethnicity versusHispanic

White 1.261 1.012–1.570 0.5255Black 0.939 0.725–1.215 0.2575Asian 1.125 0.626–2.020 0.9644

ABO versus OA 1.181 1.014–1.376 0.0002AB 3.278 2.071–5.189 <0.0001B 1.617 1.287–2.032 0.8244

Social historyCigarette use: yesversus no 1.288 1.062–1.563 0.0103

History of cocaineuse 1.981 1.591–2.467 0.3330

UNOS region versus 12 1.634 0.990–2.696 0.16543 2.983 1.781–4.997 <0.00014 2.922 1.625–5.252 0.00475 1.835 1.078–3.124 0.97616 2.670 1.368–5.211 0.09407 1.676 1.006–2.793 0.33168 1.658 0.917–2.999 0.53659 1.548 0.870–2.754 0.268710 1.564 0.940–2.601 0.091011 1.762 1.053–2.947 0.6623

LV ejection fraction 0.920 0.912–0.928 <0.00013 or more inotropicagents at the time ofincision

Yes versus no 4.859 3.396–6.952 <0.0001CPR: cardiopulmonary resuscitation; ABO: blood groups; UNOS: UnitedNetwork of Organ Sharing; LV: left ventricle.

not find a correlation between CPR donor heart utilizationand regional transplantation volumes or wait times. Thisinformation is unique to our study and has not been studied

15

20

25

30

35

40CPR donors heart utilization

(%)

Year

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

2011

2012

Figure 3: CPR donor heart procurement for transplantationbetween 2000 and 2012.

and reported before. We noted a small but encouragingdifference in utilization of CPR donor hearts over time, from28.4% in 2000 to 32.2% in 2012 (Figure 3).

With the implementation of onsite CPR protocols,including both the advanced training of emergency medicalresponse personnel and the increased availability of auto-mated electrical defibrillators to the lay public, an increasingnumber of cardiopulmonary arrest victims are receiving CPRonsite and are being brought to the hospitals for continuedresuscitation [12]. Unfortunately, a large percentage of thesepatients, as high as 70% arriving to hospitals after an onsiteresuscitation with return of spontaneous circulation, aresustaining severe permanent brain damage [13, 14] and arethen evaluated for organ donation. Over the past decade, thenumber of CPR donors have increased from 4.8% of the totaldonor pool in the year 2000 to 9.1% in the year 2012 (Figure 1);a 90% increase over time [2]. However, concerns remainregarding the optimal posttransplantation outcomes fromCPR donors [9, 15], despite multiple studies demonstratingnoninferior outcomes after heart transplantation from suchdonors [6, 16]. Presently, only one-third of the potentialCPR donor hearts are procured for heart transplantation [2].However, there has been an upward trend in accepting heartsfrom these donors (Figure 3).

Donor factors associated with suboptimal posttransplan-tation outcomes have been studied extensively. Older donorage [5, 10], hypertension, low EF [10, 17], diabetes [11, 17],excess alcohol intake [18], and cigarette smoking [19] areamong thewell-established risk factors. In our study, presenceof these factors among the CPR donors was associatedwith less procurement rates of hearts for transplantation,correlating with the published literature.

Donor gender significantly influences the heart utiliza-tion rate. In our study, we noted male CPR donor heartprocurement of 34% as compared to female donor heartprocurement of only 23%; this, too, is consistent with most ofthe other studies. In a large study of over 1800 organ donors,72% of male donor organs were utilized for transplantationas compared to 28% of female donor organs [10]. The maledonor gender preference is primarily influenced by the largermale donor body size that matches well for most male and forall female recipients. Additionally, heart transplantation fromfemale donors has been associated with less than optimal


posttransplantation outcomes, both early and late, especiallyif the recipients were male [20].

An organ donor’s cause of death has been known toinfluence posttransplantation outcomes. In particular, deathresulting from cerebrovascular accidents and intracranialbleeding is associated with poor posttransplantation out-comes [10, 21]. This explains the low percentage utilizationof hearts from the CPR donors with strokes in our study. Thelikely explanation for this observation is that perhaps thosedonors who develop massive strokes tend to be relativelyolder and carry significant cardiovascular risk factors, suchas hypertension and diabetes. Both of these factors areassociated with inferior posttransplantation outcomes.

Studies on mechanism of injury leading to brain deathshow that this also influences donor organ utilization.Trauma victims constitute 55% to 74% of organ donors [22].In a study by Kutschmann et al., besides older donor age,nontraumatic causes of death were associated with decreasedrecipient postheart transplant survival with an odds ratioof 1.48 [23]. Similarly, another study demonstrated thattraumatic head injury leading to brain death is associatedwith higher donor organ utilization: 61% versus 22% fordonors without head injury as a cause of brain death [10].Our study’s findings also suggest similar CPR donor heartprocurement from both traumatic injury donors and donorswith head trauma leading to brain death.

Organ donation rates differ among ethnic groups and areinfluenced by cultural beliefs and practices. In our study, weobserved different rates of CPR donor heart procurementfor transplantation by ethnicity. Donor heart procurementfor transplantation fromHispanics, African Americans, Cau-casians, and Asian ethnic groups was 37%, 33%, 27%, and24%, respectively. This disparity in donor heart selectionwas also noted in another study where proportionately moreHispanic (30%) and fewer Asian donors (5%) were selectedfor heart procurement for transplantation following braindeath compared to other ethnicities studied [10]. In ourstudy, higher prevalence of head trauma (35%), male gender(62%), and blood group O (60%) was noted in Hispanicethnicity heart donors compared to other heart donors; it ispossible that these attributes in isolation or in combinationhave contributed to higher heart procurement fromHispanicethnicity heart donors.

The most common blood group among US populationis O (44%) followed by A (42%), B (10%), and AB (4%).Since donors and recipients are matched primarily by bloodgroups, it is expected that donors with O blood group (so-called universal donors) would be utilized most frequently.Heart procurement for transplantation among CPR donorsin our study is consistent with this expectation.

Transplantation volumes and duration of wait timeson the transplantation list vary at different centers anddepend on the prevalence of heart failure within the patientpopulation, the number of competing programs in theregion, and, most importantly, the surrounding population.Posttransplantation outcomes have been linked to a center’stransplantation volume, with low volume centers showinginferior survival [24]. In a study by Hosenpud et al., thecritical heart transplantation center volume was nine per

year; below this, survival outcomes were considered poor[25]. In another study by Kilic et al., institutional factorswere also identified as contributing to inferior posttrans-plantation outcomes [26]. There, the authors suggest thatthe “heart transplantation center’s volume” should not bethe sole indicator of center’s quality in heart transplanta-tion. When donor risk factors were taken into account andposttransplantation outcomes were compared to transplantcenter volumes, it was clear that the low-volume centersdid poorly with high-risk donors [26]. The difference inposttransplantation outcome persisted even when both therecipient risk factors and the institutional factors were takeninto account. When stratified by the recipient risk scores,the posttransplantation outcomes appear profoundly worsein transplantation of extended criteria donors to high-riskrecipients. The authors concluded that consolidating the useof extended criteria donors to higher volume centers mightbe prudent in improving postheart transplantation outcomesin high-risk recipients. The findings of the Kilic et al. studyshould be interpreted with caution, as the donor variablesstudied were few and transplant volumes defined as “low”were below 14 heart transplants per year. To follow thisrecommendation, it would prohibit greater than 77% of hearttransplantation centers in theUS fromusing high-risk donors[19]. In the same study, extended criteria donor utilizationvaried by the UNOS regions, with Region 8 utilizing 11.4% ofmarginal donors compared to 24.7% in Region 9 [26]. In ourstudy, the highest percentage utilization of CPR donor heartswas in Region 1 (37%) and the lowest was in Region 3 (24%).We believe the difference in our results stems from differentdefinitions of donor heart utilization: high-risk versus CPRdonors. Time on 1A status varied significantly among the 11regions, from a median of 35 days in Region 5 to 90 daysin Region 7. It is possible to assume that the regions withlongerwait timeswould likely accept extended criteria donorsmore often, including those who received CPR. In our study,however, longer wait times in regions did not correlate withincreased CPR donor heart utilization. Similarly, our findingson the CPR donor heart utilization by population per hearttransplantation performed in the 11 regions did not supportany correlation between population dense regions and CPRdonor heart utilization.

5. Study Limitations

Limitations inherent to retrospective data analysis are appli-cable to our study. The primary data source for our studyis a composite UNOS database from more than 150 UStransplantation centers. Completeness of all data fields iswanted and is not always available in the database. However,its merit lies in the fact that large, pooled data from differenttransplant centers eliminate biases associated with individualcenter practices. Thus, certain generalizations can be madeof the results with regard to practicality of its usage andreproducibility. Since our focus was on the characteristicsof CPR donors only, this limited the study population to11% of the total donor pool, thus eliminating a majorityof donors from our analysis. Since CPR donors comprise


a potential group of underutilized heart donors, we felt it isimportant that we focus on this small but important groupof donor hearts. We used the large UNOS database to helpdefine donor characteristics that were associated with heartprocurement for transplantation with the hope that in futureat least CPR donor hearts with similar characteristics wouldbe utilized more frequently for transplantations. Acceptinga heart from an extended criteria donor also depends onthe medical condition and acuity of illness of the recipient.The present study has not taken the recipient factors intoconsideration when defining CPR donor heart utilization. Inour previous study of CPRheart donors, we noticed thatmoreCPR donors were matched to recipients with high acuity ofillness at transplantation, such as those with status 1A listing,those that were admitted to the hospital at transplantation,and those that were supported in an intensive care uniton life-sustaining support [6]. Despite the higher acuity ofillness in the recipients, the use of selected CPR donor heartsdid not negatively influence the intermediate or long-termoutcomes of heart transplantation. Transplantation centerpractices do change over time with changes in leadership,philosophy, and patient population. We did not study thetemporal changes in CPR donor heart utilization over timefor each transplant region, or for each transplant center.Withover 150 transplantation centers in 11 UNOS regions, we feelthat 15 years of temporal data would be both cluttered inpresentation and not very meaningful to the reader.

6. Conclusions

CPR donors are an expanding group of potential, yetpresently underutilized, heart donors. With improvementsin onsite resuscitative measures, more patients are regainingspontaneous circulation after CPR. However, if irreversibleneurologic damage is sustained, these patients become eligi-ble for organ donation. Though the clinical outcomes fromaccepting hearts from these donors are comparable, theoverall utilization of these donor hearts is only 28.8%. Donorcharacteristics such as younger age, male gender, absenceof hypertension, smoking history, traumatic head injury,and shorter CPR duration are associated with higher heartprocurement rates for transplantation. Regional factors doplay a role in donor heart selection, but it does not seemto be associated with either recipient wait times or regionaltransplantation volumes. It is our hope that in the future CPRdonor hearts with attributes associated with successful heartprocurement for transplantation will not be passed up andthat serious efforts will be made to accept these hearts, thushelping patients waiting desperately for transplantation.

Conflict of Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper.

Acknowledgments

The authors are indebted to the UNOS for providing thevaluable data for analysis. The authors thank Mr. AdamGoodreau for his expert assistance in editing the paper.

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